Inflammatory Markers: The Present, Past, and Future

The April issue of Pediatrics in Review contains an informative and valuable In Brief on inflammatory markers by Drs Viviano and Huntwork. It succinctly summarizes the individual characteristics of inflammatory markers and presents a useful table. Dr Fu, in her comment, makes an excellent point about the informed and judicious use of inflammatory markers; the availability of multiple inflammatory markers has engendered unnecessary co-ordering. This is particularly true for co-orders of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests. Reducing unnecessary co-ordering was the focus of the Choosing Wisely campaign and has resulted in documented successful interventions.¹ The In Brief makes clear why ordering the CRP alone is preferred in the vast majority of circumstances but also why ordering both could occasionally be justified due to the diagnostic value of their discrepant results in some conditions. Sorry, there’s no spoiler here!

During the majority of my career, the ESR was all we had. This made me reflect on how we often sought diagnostic clues about inflammatory conditions in the CBC results and in the total protein and albumin concentrations. These clues corroborated and added specificity to the ESR result, and they continue to be valuable adjuncts to the interpretation of the newer inflammatory markers. For early-stage trainees and students, I created an abbreviated table of findings in routine lab results associated with inflammation and associated etiologies (below).

Regarding the future of inflammatory markers, Bhargava et al² describe an AI-driven, FDA approved, 22 component adult sepsis risk score. Of note, the 22 components include not only laboratory test results but also clinical signs and the patient’s age. Relevant to inflammatory markers, the top 5 features ranked by their importance to the sepsis score include the procalcitonin level as number 1 and platelet count as number 4. Number 22 is the white blood cell count! I found the plot of the 22 features’ individual importance to the score to be very interesting. Mills, Watson, and Waterfield³ describe a framework for using “omics” to discover novel biomarkers of pediatric sepsis. In this article, the authors advance the idea that genomics could be employed to discover gene variants that confer risk for sepsis, transcriptomics could be used to examine gene expression patterns in early sepsis, proteomics could identify novel protein markers, and metabolomics could assess metabolites that could guide the need to escalate or de-escalate therapy in sepsis.

Finally, while it is very likely that the development of new inflammatory markers and their implementation will undergo very rapid progress in the coming years, the ESR, having served us for over 100 years, will still retain value as one of the few lab tests that can be done during a power outage!

Table: Selected Inflammatory Signals in Routine Lab Tests

Abbreviations. SLE Systemic Lupus Erythematosus. HLH Hemophagocytic Lymphohistiocytosis. MAS Macrophage Activation Syndrome. RSV Respiratory Syncytial Virus, IBD Inflammatory Bowel Disease. TP Total Protein

References

1. Cho HJ, Talledo J, Alaiev D, et al. Choosing Wisely and reducing the simultaneous ordering of erythrocyte sedimentation rate and C-reactive protein testing in a large safety net system. Am J Clin Pathol. 2023;160(6):585-592. doi:10.1093/ajcp/aqad093
2. Bhargava, Akhil, et al. "FDA-Authorized AI/ML Tool for Sepsis Prediction: Development and Validation." NEJM AI12 (2024): AIoa2400867.
3. Rodgers O, Mills C, Watson C, Waterfield T. Role of diagnostic tests for sepsis in children: a review. Arch Dis Child. 2024 Sep 25;109(10):786-793. doi: 10.1136/archdischild-2023-325984. PMID: 38262696.